Cationic anticancer peptide L-K6-modified and doxorubicin-loaded mesoporous silica nanoparticles reverse multidrug resistance of breast cancer

Haiting Sun; Shaodan Dong; Lingying Kong; Rongchun Wang; Jiaqi Zhao; Yue Guan; Che Wang; Dejing Shang

Arabian Journal of Chemistry (May 2024)

Cationic anticancer peptide L-K6-modified and doxorubicin-loaded mesoporous silica nanoparticles reverse multidrug resistance of breast cancer

Haiting Sun,
Shaodan Dong,
Lingying Kong,
Rongchun Wang,
Jiaqi Zhao,
Yue Guan,
Che Wang,
Dejing Shang

Affiliations

Haiting Sun: Department of Medicinal Chemistry, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China; Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116081, China
Shaodan Dong: Department of Medicinal Chemistry, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China; Zhuanghe No.30 Junior Middle School, Dalian 116499, China
Lingying Kong: Department of Medicinal Chemistry, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China
Rongchun Wang: Department of Medicinal Chemistry, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China
Jiaqi Zhao: Department of Medicinal Chemistry, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China
Yue Guan: Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116081, China; School of Life Science, Liaoning Normal University, Dalian 116081, China
Che Wang: Department of Medicinal Chemistry, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China; Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116081, China; Corresponding authors.
Dejing Shang: Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116081, China; School of Life Science, Liaoning Normal University, Dalian 116081, China; Corresponding authors.

Journal volume & issue: Vol. 17, no. 5
p. 105735

Abstract

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Multidrug resistance (MDR) is the major challenge for chemotherapy of cancer and makes the treatment benefits unsustainable. To overcome this issue, nanotechnology has been introduced and various nanocarriers have been constructed to reverse MDR in drug resistant cancer cells. Here, mesoporous silica nanoparticle (MSN-COOH) were modified with cationic anticancer peptide L-K6 (MSN@L-K6), and further loaded with doxorubicin (DOX) to construct an anticancer nano-system, MSN@L-K6@DOX. Our results showed that MSN@L-K6@DOX released DOX in pH-sensitive manner, which enable to be highly efficient in delivering drugs to tumors, counterbalancing the MDR. In addition, MSN@L-K6@DOX treatment decreased the expression level of P-glycoprotein in MCF-7/ADR cells, enhanced the intracellular accumulation of DOX, and thereafter reversed the MDR of MCF-7/ADR cells to DOX. Moreover, the MDR reversal activity of MSN@L-K6@DOX was further confirmed in xenograft mouse model, as evidenced by the decreased tumor volume and weight. These results indicate the MDR reversal activity of MSN@L-K6@DOX and may provide a novel strategy for the development of nano-based drug delivery system to overcome cancer MDR.

Published in Arabian Journal of Chemistry

ISSN: 1878-5352 (Print)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Chemistry
Website: http://www.journals.elsevier.com/arabian-journal-of-chemistry/

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